The grand challenge addressed by the Penn Implementation Science Center in Cancer Control (Penn ISC3) is to apply insights from behavioral economics to accelerate the pace at which evidence-based practices for cancer care are deployed to improve outcomes for individuals with cancer. Penn offers a unique environment in which to conduct this paradigm-shifting work, given our expertise in implementation science, behavioral economics, and innovative cancer care delivery. The complementary and multi-disciplinary expertise of the three MPIs (Bei- das, Bekelman, Schnoll), coupled with existing Penn resources, including the Penn Center for Cancer Care Innovation [PC3I], the Center for Health Incentives and Behavioral Economics [CHIBE], and the Penn Imple- mentation Science Center at the Leonard Davis Institute [PISCE@LDI], represent a unique opportunity to ad- vance the quality of cancer care. The Administrative Core, led by Drs. Beidas, Bekelman, and Schnoll, will ensure that the activities of Penn ISC3 are coordinated, synergistic, and congruent with timelines. The Implementation Laboratory, led by Drs. Bekelman and Shulman, represents a diverse ecosystem that includes five hospitals and linked clinical sites, with over 200 oncologists that serve over 15,000 unique new patients annually. Our Research Program, led by Drs. Beidas and Buttenheim, will oversee the development and testing of implementation strat- egies that target patients and clinicians within our Implementation Lab and are centered on the idea of ?nudging? for optimal implementation and effectiveness outcomes. The Research Program includes investigators with ex- pertise in implementation science, behavioral economics, cancer care delivery research, healthcare innovation, measurement, and mixed methods. In the first two years, we propose three Signature Pilot Projects and two Methods Projects with a commitment to rapid learning that will allow Penn ISC3 to be optimally nimble. Signature Pilot Project 1 (Jenssen/Leone) tests patient- and clinician-directed implementation strategies to increase referral to tobacco cessation programs among cancer patients. Signature Pilot Project 2 (Bekelman/Patel) tests patient- and clinician-directed implementation strategies to increase higher-value bone modifying agents in patients with breast, lung, and prostate cancer. Common methods and measures are linked to allow for pooling of data and to accomplish our objectives of testing multilevel implementation strategies and mechanisms across contexts. Our exploratory and high-reward Signature Pilot Project 3 (Bekelman/Rendle) will test a patient-directed imple- mentation strategy that leverages artificial intelligence and machine learning to promote oral chemotherapy ad- herence and symptom management. Two methods projects, in support of the Projects, will advance the science of implementation methods. Methods Project 1 will develop a toolkit for the application of rapid cycle approaches (Asch/Buttenheim); Methods Project 2 will use qualitative comparative analysis to characterize multilevel con- textual variation (Barg/Rendle). The Penn ISC3 has the potential to identify novel, disseminable, and scalable ways to advance the quality of cancer care and improve the health outcomes for individuals with cancer. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page